Cargando…
The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage
P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NA...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267345/ https://www.ncbi.nlm.nih.gov/pubmed/35806450 http://dx.doi.org/10.3390/ijms23137447 |
_version_ | 1784743696649945088 |
---|---|
author | Rossi, Chiara Salvati, Antonio Distaso, Mariarosaria Campani, Daniela Raggi, Francesco Biancalana, Edoardo Tricò, Domenico Brunetto, Maurizia Rossana Solini, Anna |
author_facet | Rossi, Chiara Salvati, Antonio Distaso, Mariarosaria Campani, Daniela Raggi, Francesco Biancalana, Edoardo Tricò, Domenico Brunetto, Maurizia Rossana Solini, Anna |
author_sort | Rossi, Chiara |
collection | PubMed |
description | P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. |
format | Online Article Text |
id | pubmed-9267345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92673452022-07-09 The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage Rossi, Chiara Salvati, Antonio Distaso, Mariarosaria Campani, Daniela Raggi, Francesco Biancalana, Edoardo Tricò, Domenico Brunetto, Maurizia Rossana Solini, Anna Int J Mol Sci Article P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage. MDPI 2022-07-04 /pmc/articles/PMC9267345/ /pubmed/35806450 http://dx.doi.org/10.3390/ijms23137447 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rossi, Chiara Salvati, Antonio Distaso, Mariarosaria Campani, Daniela Raggi, Francesco Biancalana, Edoardo Tricò, Domenico Brunetto, Maurizia Rossana Solini, Anna The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title | The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title_full | The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title_fullStr | The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title_full_unstemmed | The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title_short | The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage |
title_sort | p2x7r-nlrp3 and aim2 inflammasome platforms mark the complexity/severity of viral or metabolic liver damage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267345/ https://www.ncbi.nlm.nih.gov/pubmed/35806450 http://dx.doi.org/10.3390/ijms23137447 |
work_keys_str_mv | AT rossichiara thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT salvatiantonio thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT distasomariarosaria thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT campanidaniela thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT raggifrancesco thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT biancalanaedoardo thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT tricodomenico thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT brunettomauriziarossana thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT solinianna thep2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT rossichiara p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT salvatiantonio p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT distasomariarosaria p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT campanidaniela p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT raggifrancesco p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT biancalanaedoardo p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT tricodomenico p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT brunettomauriziarossana p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage AT solinianna p2x7rnlrp3andaim2inflammasomeplatformsmarkthecomplexityseverityofviralormetabolicliverdamage |